In a search for a system with which to study the mechanisms of protein degradation, the specific activity of the NADPH-dependent glutamate dehydrogenase of Saccharomyces cerevisiae was found to drop to 30% of its initial value upon glucose starvation of glucose grown cells. The modification leading to the loss in specific activity is irreversible as demonstrated by the necessity of "de novo" protein synthesis for recovery of the activity. The loss of specific activity has been shown to be inhibited by energy uncouplers, inhibitors of protein synthesis and a serine protease inhibitor.